473 research outputs found

    Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia

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    An elevated neutrophil–lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated with cachexia, the terminal wasting syndrome. Here, using murine model systems of colorectal and pancreatic cancer we show that neutrophilia in the circulation and multiple organs, accompanied by extramedullary hematopoiesis, is an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumor-bearing animals utilize aerobic glycolysis, similar to cancer cells. Although pharmacological inhibition of aerobic glycolysis slows down tumor growth in C26 tumor-bearing mice, it precipitates cachexia, thereby shortening the overall survival. This negative effect may be explained by our observation that acute depletion of neutrophils in pre-cachectic mice impairs systemic glucose homeostasis secondary to altered hepatic lipid processing. Thus, changes in neutrophil number, distribution, and metabolism play an adaptive role in host metabolic homeostasis during cancer progression. Our findings provide insight into early events during cancer progression to cachexia, with implications for therapy

    A coupled method for initializing El Niño Southern Oscillation forecasts using sea surface temperature

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    A simple method for initializing coupled general circulation models (CGCMs) using only sea surface temperature (SST) data is comprehensively tested in an extended set of ensemble hindcasts with the Max-Planck-Institute (MPI) climate model, MPI-OM/ECHAM5. In the scheme, initial conditions for both atmosphere and ocean are generated by running the coupled model with SST nudged strongly to observations. Air–sea interaction provides the mechanism through which SST influences the subsurface. Comparison with observations indicates that the scheme is performing well in the tropical Pacific. Results from a 500-yr control run show that the model's El Niño Southern Oscillation (ENSO) variability is quite realistic, in terms of strength, structure and period. The hindcasts performed were six months long, initiated four times per year, consisted of nine ensemble members, and covered the period 1969–2001. The ensemble was generated by only varying atmospheric initial conditions, which were sampled from the initialization run to capture intraseasonal variability. At six-month lead, the model is able to capture all the major ENSO extremes of the period. However, because of poor sampling of ocean initial conditions and model deficiencies, the ensemble-mean anomaly correlation skill for Niño3 SST is only 0.6 at six-month lead. None the less, the results presented here demonstrate the potential of such a simple scheme, and provide a simple method by which SST information may be better used in more complex initialization schemes

    N-ftaloil-glicin-hidroksamska kiselina kao kelator željeza u serumu štakora

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    The aim of this study was to investigate the activity of N-phthaloyl-glycine-hydroxamic acid (Phth-Gly-HA) as a new iron chelator in vivo to be used in iron overload diseases. After intraperitoneal application of Phth-Gly-HA to male rats (1 mg kg1 body mass) once a day for seven days, iron serum level decreased by 21%, whereas the iron value dropped by 32% in female rats (1.5 mg kg1 body mass). The results indicate that the tested substance has the ability to bind serum iron by complexation. Besides transferrin iron release, mobilization of ferritin iron is also possibleU cilju pronalaženja novog efikasnog kelatora koji bi mogao poslužiti u liječenju bolesti izazvanih viškom željeza, u ovom je radu ispitano djelovanje N-ftaloil-glicin-hidroksamske kiseline (Phth-Gly-HA) in vivo. Istraživan je utjecaj kelatora na razinu željeza u serumu štakora nakon intraperitonealne primjene vodene otopine Phth-Gly-HA (0,1 mg mL1) jednom dnevno tijekom 7 dana. Kontrolne su životinje primale fiziološku otopinu. Kod mužjaka injektiranje test supstancije (1 mg kg1) uzrokovalo je pad serumskog željeza za 21%. Kod ženki je nakon tretmana (1,5 mg kg1) izmjereno sniženje razine željeza za 35%. Rezultati pokazuju da ispitivana supstanca ima sposobnost kompleksiranja serumskog željeza, pretežno transferinskog, ali da postoji mogućnost mobilizacije željeza i iz feritinskih zaliha

    Oxygenated Aromatic Compounds are Important Precursors of Secondary Organic Aerosol in Biomass Burning Emissions

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    Biomass burning is the largest combustion-related source of volatile organic compounds (VOCs) to the atmosphere. We describe the development of a state-of-the-science model to simulate the photochemical formation of secondary organic aerosol (SOA) from biomass-burning emissions observed in dry (RH <20%) environmental chamber experiments. The modeling is supported by (i) new oxidation chamber measurements, (ii) detailed concurrent measurements of SOA precursors in biomass-burning emissions, and (iii) development of SOA parameters for heterocyclic and oxygenated aromatic compounds based on historical chamber experiments. We find that oxygenated aromatic compounds, including phenols and methoxyphenols, account for slightly less than 60% of the SOA formed and help our model explain the variability in the organic aerosol mass (R² = 0.68) and O/C (R² = 0.69) enhancement ratios observed across 11 chamber experiments. Despite abundant emissions, heterocyclic compounds that included furans contribute to ∼20% of the total SOA. The use of pyrolysis-temperature-based or averaged emission profiles to represent SOA precursors, rather than those specific to each fire, provide similar results to within 20%. Our findings demonstrate the necessity of accounting for oxygenated aromatics from biomass-burning emissions and their SOA formation in chemical mechanisms

    Recommendations for digitally recording, recirculating, and remixing holocaust testimony

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    Testimony has always raised ethical issues, especially in relation to questions of provenance, integrity, ownership, and authenticity. Nevertheless, it has become one of the most powerful sources for Holocaust education. Meeting a Holocaust survivor in-person has been a particular tenet of educational experiences. Looking forward, we face dual challenges: (1) the decline in numbers of living witnesses to the Holocaust, (2) the increasing prevalence of digital technologies. It has been somewhat taken for granted that the latter offers solutions for dealing with the former. Media technologies have been integral to the dissemination of Holocaust testimony since the 1940s. From the attempts to smuggle out material evidence of witnessing atrocities on photographic film to the scraps of paper and writing implements used to document experiences and wishes for the future, from the Oneg Shabbat archives of the Warsaw Ghetto to the 'Scrolls of Auschwitz'. It is however in the immediate post-war period with Boder's wire recordings that spoken testimony of events after the fact began to be recorded at scale. Some survivors later chose to publish their testimonies in memoir form. Then, in 1979, the Holocaust Survivors Film Project launched which developed into the Fortunoff Archives at Yale University. At Yale, audio-video testimonies were captured on tape, which not only preserved the speech patterns alongside narrative content of testimonies, but gestures and body language also. In moments of silence, viewers of testimony could now see the testimony-giver's body, any emotional reaction, and their gaze. There was a range of academic writing (from Lawrence Langer to Georges Agamben and Jean-François Lyotard) that addressed the significance of these 'silences', in different ways. With video then digital interventions in testimony recording, there has been increasingly attention given to the visual elements of testimonial narratives. This has been particularly demonstrated by the projects of the USC Shoah Foundation. Starting in a similar vein to Fortunoff, with audio-visual testimonies, the Foundation (initially established by the profits for Schindler's List (1994)), has since turned its attention to interactive interfaces (IWitness) use of machine learning (Dimensions in Testimony) and virtual reality ('Lola' and 'The Last Goodbye') and 360-degree on-location testimonies to explore the affordances that emerging technologies can offer for the sustainability of testimony into the future. Whilst of course, historical concerns about testimony will always remain, digital technologies introduce new possibilities and challenges, which needs to be better understood across the sector. This report serves as an important first step in this work. It was created as part of the research project 'Participatory Workshops - Co-Designing Standards for Digital Interventions in Holocaust Memory and Education', which is one thread of the larger Digital Holocaust Memory Project at the University of Sussex. The participatory workshops have focused on six themes, each of which brought together a different range of expertise to discuss current challenges and consider possible recommendations for the future. The themes were: • AI and machine learning • Digitising material evidence • Recording, recirculating and remixing testimony • Social media • Virtual memoryscapes • Computer games In this report, you will find the recommendations and a suggestion of who could bear responsibility to take each of these on; a summary of the workshop discussions; and a list of the participants who contributed to this work. There will also be a complementary action plan published alongside this report. The recommendations and discussion presented here summarise participant opinions, which might not reflect the opinions of project leads or any individual participant in full, or all participants in consensus. Whilst we have offered participants the opportunity to review and discuss the development of these guidelines, we have tried to retain differing perspectives rather than suggest there was homogeneity in opinion. The discussion presented is an aggregation of professional opinions informed by a diverse range of experiences and expertise. We present ideas collectively, rather than attributing specific points to participants. All participants are, however, acknowledged as contributors to this report. This document does not claim to be the last word on digitally recording, recirculating, and remixing Holocaust testimony, rather we recognise that this is very much the beginning of a longer conversation. We hope that the immediate recommendations suggested in these guidelines will help organisations and individuals to prioritise the work needed to work effectively with Holocaust testimony in digital spaces

    Employing Relative Entropy Techniques for Assessing Modifications in Animal Behavior

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    In order to make quantitative statements regarding behavior patterns in animals, it is important to establish whether new observations are statistically consistent with the animal's equilibrium behavior. For example, traumatic stress from the presence of a telemetry transmitter may modify the baseline behavior of an animal, which in turn can lead to a bias in results. From the perspective of information theory such a bias can be interpreted as the amount of information gained from a new measurement, relative to an existing equilibrium distribution. One important concept in information theory is the relative entropy, from which we develop a framework for quantifying time-dependent differences between new observations and equilibrium. We demonstrate the utility of the relative entropy by analyzing observed speed distributions of Pacific bluefin tuna, recorded within a 48-hour time span after capture and release. When the observed and equilibrium distributions are Gaussian, we show that the tuna's behavior is modified by traumatic stress, and that the resulting modification is dominated by the difference in central tendencies of the two distributions. Within a 95% confidence level, we find that the tuna's behavior is significantly altered for approximately 5 hours after release. Our analysis reveals a periodic fluctuation in speed corresponding to the moment just before sunrise on each day, a phenomenon related to the tuna's daily diving pattern that occurs in response to changes in ambient light
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